Osteoarthritis (OA) is a degenerative joint disease characterized by a fragmentation and erosion of the articular cartilage, which becomes soft, frayed and thinned with alteration of the subchondral bone, hypertrophy of the bone, including outgrowths of marginal osteophytes and changes accompanied by pain and stiffness, and finally by loss of function. Osteoarthritis mainly affects the weight bearing joints. When clinically evident, osteoarthritis is a major cause of morbidity and disability, especially for the elderly, due to joint pain, morning stiffness, and limitation of movement and commonly involves the neck, lower back, knees, hips and joints of the fingers (Lawrence et al., Arthritis Rheum., 41:778-99, 1998; Ling et al., J. Am. Geriatr. Soc. 46:216-25, 1998). Osteoarthritis can also develop in joints that have suffered injury or trauma in the past, or have been subjected to prolonged heavy use.
Conventional radiography is generally considered the gold standard for the diagnosis and classification of OA, despite its insensitivity to predict clinical symptoms and its insensitivity to detect early disease or subtle changes over time (Lethbridge-Cejku et al., Arthritis Care Res. 8:182-83, 1995; Altman et al., Arthritis Rheum. 30:1214-25, 1987). The search for biomarkers measured in synovial fluid, serum, or urine that can be used for diagnosis or for predicting the clinical course of the disease has intensified over recent years. Initial studies focused on cartilage precursors, constituents and degradation products (Bruyere et al., J Rheumatol. 30:1043-50, 2003; Dragomir et al., Osteoarthritis Cartilage 10:687-91, 2002; Lohmander et al., Arthritis. Rheum. 42:534-44, 1999; Poole, Arthritis. Rheum. 46:2549-52, 2002; Poole et al., J. Immunol. Meth. 294:145-53, 2004; Clark et al., Arthritis. Rheum. 42:2356-64, 1999; Vilim et al., Osteoarthritis Cartilage 10:707-13, 2002). However, identification of other OA markers is needed, because currently available markers only reflect cartilage and bone damage that have already occurred. Therefore, the identification of markers that reflect early events, predisposition to OA, or factors involved in the continued disease process, would be useful for example to identify patients that could benefit from early intervention of OA. In addition, identification of OA biomarkers may permit the identification of novel therapeutic targets.